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Biomedical subjects

M Iizuka

Publications and source records attributed to M Iizuka.

At least 91 records · Page 5Linked to original sources

Development of locomotor activity induced by NMDA receptor activation in the lumbar spinal cord of the rat fetus studied in vitro.

The development of neuronal circuits generating locomotor activity was characterized in an isolated lumbar spinal cord preparation from of fetal and neonatal rats. Locomotor activity induced by bath application of the NMDA receptor agonists, NMA and NMDA, was monitored from both sides of the corresponding lumbar ventral roots. Activation of NMDA receptors first evoked rhythmic motor activity at E15.5. NMA-induced rhythmic motor activity was not observed under synaptic blockade by TTX or cadmium ions, suggesting that this activity was evoked by synaptic drive from the interneuronal circuits in the spinal cord. At E15.5-E16.5, the rhythmic motor activity on both sides was synchronized. Phase relationship of the rhythmic motor activity between both sides was variable at E17.5-E19.5. The rhythmic motor activity was alternating on both sides at E20.5. Mid-sagittal splitting of the spinal cord did not affect the rhythm generation at all stages examined, suggesting the existence of independent rhythm-generating circuits on each side. The rhythmic motor activity in the presence of strychnine was synchronized on both sides at all stages examined. These results indicate that the changes in rhythm pattern are mediated by development of glycinergic inhibitory pathways, while the basic rhythm can be generated without the glycinergic inhibitory pathways.

Animals↗

Spontaneous motoneuronal activity mediated by glycine and GABA in the spinal cord of rat fetuses in vitro.

1. Spontaneous motoneuronal activity was monitored from the lumbar ventral roots in an isolated spinal cord preparation from rat fetuses at embryonic days (E) 13.5-18.5. 2. Spontaneous bursts that were synchronized in both left and right ventral roots were observed periodically (mean interval, 1.5-2.6 min) from E14.5 to 17.5. This activity was abolished in Ca(2+)-free saline or by application of tetrodotoxin (1 microM), indicating that it was synaptically mediated. 3. The glutamate receptor blocker kynurenate (4 mM) failed to block spontaneous bursts at E14.5-15.5, though it completely abolished them at E17.5. The glycine receptor antagonist strychnine (10 microM) completely blocked spontaneous bursts at E14.5-15.5. Bicuculline, a GABAA receptor antagonist, reduced the amplitude of the spontaneous bursts. 4. At E15.5, a brief application of glycine (250 microM to 2 mM) evoked excitatory responses resembling the spontaneous bursts in both time course and amplitude. Such glycine-induced responses were not observed under Ca(2+)-free conditions, suggesting that they were synaptically evoked. These synaptic responses were not blocked by kynurenate (4 mM), but they were abolished by strychnine (10 microM). 5. It is concluded that glycine and GABA generate the earliest spontaneous motor activity of the fetus and function transiently as excitatory transmitters in the embryonic spinal cord.

Animals↗

Identification of domains of the cardiac inward rectifying K+ channel, CIR, involved in the heteromultimer formation and in the G-protein gating.

The cardiac inward rectifying K+ channel, CIR, and the strongly inward rectifying K+ channel, IRK1, exhibited clearly different electrophysiological properties. CIR formed a heteromultimer with the G-protein coupled inward rectifying K+ channel, GIRK1, whereas IRK1 did not, and CTR homo- and heteromultimeric channels were activated by G-protein beta 1 gamma 2 subunits (G beta 1 gamma 2), whereas IRK1 channels were not. To identify the domains of CIR involved in the heteromultimer formation with GIRK1 and in the G beta 1 gamma 2 gating, we constructed chimeras of CIR and IRK1 and examined their electrophysiological properties. The channels were divided into three domains; the N-terminal cytoplasmic domain, the C-terminal cytoplasmic domain and the residual core domain. By the analysis, it was concluded that (i) the core region of CIR, but not the N and C cytoplasmic domains, is critical for the heteromultimer formation with GIRK1; and (ii) the N and C terminal cytoplasmic regions of CIR are sufficient for the G beta 1 gamma 2 gating. We also showed that the N terminal cytoplasmic region is involved in the determination of the rate of activation upon hyperpolarization.

Animals↗

Angiographic and coronary risk factor analyses of Japanese patients with ischemic heart disease before age 40--a multicenter cooperative study.

Coronary angiographic and risk factor (RF) characteristics were analyzed in 133 Japanese patients with ischemic heart disease (IHD) who were less than 40 years old and who had undergone coronary angiography (CAG) during the past 10 years at six university hospitals in the Tokyo area. We compared the coronary angiographic characteristics of the subject group with those of 216 controls with coronary sclerosis detected by CAG who were more than 40 years old (older control group) and the RF characteristics with those of 133 sex- and age-matched volunteers (younger control group). Sixty seven percent of the subjects (89 cases) were diagnosed as having myocardial infarction (MI) and 33% (44 cases) had angina pectoris (AP). Coronary artery disorders in this group consisted of 103 (77%) cases of coronary sclerosis, 20 (15%) cases of coronary spasm and 10 (8%) cases of miscellaneous diseases, eg, possible vasculitis with connective tissue disease, congenital anomalies, etc. The incidences of significant (> or = 75%) sclerotic narrowing in 0 vessels (31%) and 1 vessel (49%) in the subject group were significantly (p < 0.01) higher than those in the older control group, while the incidence of multivessel disease was significantly (p < 0.05) less in the subject group than in the older control group. The incidences of the following coronary risk factors were significantly (p < 0.05) higher in the subjects than in the younger controls: smoking (83% vs 35%), hypercholesteremia (44% vs 10%), obesity (31% vs 9%), hypertension (29% vs 3%), familial IHD (28% vs 7%) and diabetes mellitus (19% vs 2%). Thus, zero- or single-vessel disease predominated in the younger subject group and the prevalence of coronary risk factors was significantly higher in the subject.

Adult↗

Early diagnosis and estimation of pulmonary congestion and edema in patients with left-sided heart diseases from histogram of pulmonary CT number.

To establish an early diagnosis and have a quantitative estimation of congestion or edema, pulmonary CT scans were performed to detect the increase of regional lung water volume of patients with congestive heart failure. CT scanning of the upper, middle, and lower lung fields at maximum inspiration and hemodynamic analysis to ensure a hemodynamically chronic stable condition after the heart failure therapy for 5 weeks by cardiac catheterization within 2 weeks before CT scanning were performed in 10 normal subjects and 25 patients with left-sided heart failure. Patients were divided into two groups according to the presence or absence of pulmonary congestion or edema on chest radiographs, and the mean pulmonary wedge pressure (mPWP). The pulmonary congestion group (14 patients) had pulmonary congestion or edema, and mPWP was greater than 13 mm Hg despite the heart failure therapy. The nonpulmonary congestion group (11 patients) had no pulmonary congestion or edema, and mPWP was lower than 10 mm Hg. Histograms of pulmonary CT numbers were graphed to a set region of interest (ROI) on transverse CT images in all subjects; then changes of pulmonary CT numbers when pulmonary congestion or edema occurred were estimated from those histograms. We found that when severe pulmonary congestion or edema occurred in 6 patients with severe left heart failure, the pulmonary CT numbers within the ROI rapidly increased from -650 to -750 Hounsfield units (HU). We defined the amount ratio between the pixels (pixel counts between -650 and -750 HU within these R0Is) and the pixels (pixel counts between -300 and -950 HU) of the CT number (which were all pixels composing these R0Is) x100(%) as "%PXL." %PXL showed a linear correlation with mPWP. Compared with the %PXL in the normal group, the %PXL in the pulmonary congestion group was significantly higher than that in the normal group (p<0.05, p<0.01, p<0.001) in all lung fields. Similarly, compared with the %PXL in the normal group, %PXL in the nonpulmonary congestion group was significantly higher than that in the normal group in the middle and lower lung fields (p<0.05, p<0.01) in the posterior field. From these results, we concluded that %PXL was a good index to identify abnormal water content usually not recognizable by routine chest radiograph in the lungs.

Adult↗

[A clinical evaluation of chest wall reconstruction].

From April 1987 to June 1995, we performed the chest wall reconstruction in 13 cases of 25 ones who had chest wall resection. The clinical records of these 13 patients were reviewed as follows. The histological diagnosis of these cases were direct invasion by primary lung cancer in 13 cases, malignant tumor of the chest wall in 5 cases, benign tumor or inflammation of the chest wall in 4 cases, local recurrence of the breast cancer and post operative radiation ulcer in each 1 case respectively, and mediastinal peripheral nerve sheath tumor in 1 case. Full diagnosis of the mediastinal malignant tumors were Ewing' sarcoma, chondrosarcoma, malignant lymphoma, malignant fibrous histiocytoma and eosinophilic granuloma in each 1 case respectively. The total number of resected ribs was 10 (bilateral 5 ribs with sternal body) in 1 case, 4 in 1 case, 3 in 6 cases, 2 in 2 cases and 1 in 4 cases. The following statement shows our methods of chest wall reconstructions. We treated one case with wide anterior chest wall resection, we treated by the Marlex-resin sandwich, 4 cases with 4 or 3 ribs of anterior or lateral chest wall, by sheets of Marlex mesh in layers, 3 cases with 3 ribs of posterior site, 1 case with 2 ribs and 4 cases with one rib, these 7 cases treated by cross sutures. And, we treated another 2 cases by pedicle omental flap and major pectoral muscle in each case respectively. The Marlex-resin sandwich has easy fixation and excellent stability, but it has also foreign body reaction. Therefore our case needed to remove of sandwich 10 months later for cellulitis and infection after the operation. Recently we use mostly sheets of Marlex mesh in layers, for the reconstruction of the chest wall with 3 or more rib's defect, but if it is more small defect, we use the cross suture method. The cross suture is very easy and effective method to maintain the stability of small chest wall defect.

Adolescent↗

[Pulmonary typical carcinoid with metastases to pulmonary hilar, and mediastinal lymph nodes].

A 50-year-old woman was admitted to our hospital complaining of recurrent bloody sputum and hemoptysis. Chest X-ray films showed an infiltrative shadow in the left lower lung field. Chest computed tomograms showed a nodular tumor shadow near the left B8 and this tumor shadow was found between A8 and A9 by pulmonary arteriography. Bronchoscopic examination revealed a red coagulum in the left B8 and cytologic examination of broncho alveolar lavage fluid revealed atypical squamous cells. With a clinical diagnosis of squamous cell carcinoma of the lung, a left lower lobectomy with hilar and mediastinal lymph node dissection was done. A milk-white tumor was found in the lower lobe of the resected lung. The pathological diagnosis of the resected tissue specimen was carcinoid, accompanied by pulmonary, hilar, and mediastinal lymph node metastases. Reduced immunofluorescence by Chromogranin A and serotonin staining were further evidence that the tumor was atypical. This case is very interesting in that the tumor metastasized to the lung and lymph nodes, even-though it was pathologically typical.

Carcinoid Tumor↗

[Deletion map of human chromosome 11 in lung cancers].

The relatively frequent loss of heterozygosity at loci on the short arm of chromosome 11 in lung cancers has suggested the presence of a putative tumor suppressor gene. For location of the gene, a fine deletion map of human chromosome 11 was constructed by analysis of 79 lung cancers with 31 sequence-tagged-site markers that dotted chromosome 11 and detected polymorphic changes in nucleotide sequences. The results showed that three regions, 11p12-p15, 11q12, and 11q14-q24, were commonly deleted in a considerable number of cancers, indicating the possible presence of more than one tumor suppressor gene.

Chromosome Deletion↗

[Abnormal branching of left pulmonary artery to the lateral and posterior basal segments].

A 70-year-old male, underwent left lower lobectomy due to lung cancer, had an extremely rare form of left pulmonary artery branching. His pulmonary artery supplying to lateral and posterior basal segments (A9 + 10) was arisen anteriorly from the root of the left pulmonary artery in the mediastinum and ran below in the anterior portion of the upper lobe stem bronchus. Embriologically, this abnormality might be due to a derangement of anastomosis between the pulmonary arch system and splanic plexus in primitive lung, and was interpreted as one of the pulmonary sequestration. Clinically, particularly at thoracotomy, the presence of a large vessel in an unexpected location is very hazardous, so that preoperative pulmonary angiography is useful to detect the abnormal branching.

Aged↗

[Cavitary lung cancer with a fungus ball-like shadow].

A 75-year-old woman had an irregularly shaped cavitary lesion in the right upper lung field on a chest X-ray film and a CT scan. Primary lung cancer was suspected, but no evidence of malignancy or of infection was found on examination of specimens obtained by transbronchial biopsy and by lavage. Seven months after the first examination the cavity was found to have enlarged and an intra-cavitary fungus ball like shadow was seen. On the basis of these findings, pulmonary aspergilloma with or without primary lung cancer was suspected. Examination of a specimen obtained by transbronchial biopsy revealed squamous cell carcinoma. Right upper lobectomy was done, and the resected tissue included a polypoid nodule and a cavity wall composed of a milky-white solid tumor. Microscopic examination revealed a moderately differentiated squamous cell carcinoma in both the cavity wall and the polypoid nodule, and no evidence of fungal involvement.

Aged↗

Loss of heterozygosity at 11p15 in malignant glioma.

Deletions of loci on chromosome 11p have been found frequently in several malignant tumors including gliomas, suggesting the presence of tumor suppressor genes. We analyzed 38 gliomas [26 malignant gliomas (grades III and IV) and 12 less malignant gliomas (grade I and II)] for loss of heterozygosity using microsatellite sequences on 11p as polymorphic markers. Loss of heterozygosity was found in 8 of 26 malignant gliomas (31%) but not in the less malignant gliomas. In the region with loss of heterozygosity, loci on 11p15.5-pter were commonly deleted. Our results suggest that a putative tumor suppressor gene involved in malignant progression of gliomas is located in an approximately 21-cM region on 11p15.5-pter.

Base Sequence↗

Allelic losses in human chromosome 11 in lung cancers.

The relatively frequent loss of heterozygosity at loci on the short arm of chromosome 11 in human lung cancers has suggested the presence of a putative tumor suppressor gene. For location of the gene, a fine deletion map of human chromosome 11 was constructed by analysis of DNAs from 79 lung cancers with 31 sequence-tagged-site markers that dotted chromosome 11 and detected polymorphic changes in nucleotide sequences. The results showed that three regions, 11p12-p15, 11q12, and 11q14-q24, were commonly deleted in a considerable number of cancers, indicating the possible presence of more than one tumor suppressor gene. The range of deletion in the 11p15 region was estimated to be 4.5 megabases. That in the 11q24-q24 region was divided into two portions: one was 3 cM in length, and the other was longer and could not be specified because of lack of appropriate markers. The deletion in the 11q12 region was so short that two markers flanking the region could not be identified by genetic analysis.

Alleles↗

[Multiple eccrine spiradenoma. Histological association with dermal cylindroma].

A case of multiple eccrine spiradenomata is reported. One of the tumours was histopathologically associated with dermal cylindroma, and immunohistochemical studies showed that the cylindroma cells differentiate towards the secreting portion of the eccrine sweat gland. The relationship among multiple eccrine spiradenomata, dermal cylindroma and multiple trichoepitheliomata is discussed.

Adenoma↗

Radiosensitivity and cell cycle redistribution of cultured human tumour cells during fractionated daily 2-Gy irradiations.

Exponentially growing SQ-5 human lung squamous cell carcinoma cells were irradiated in vitro at 2-Gy per fraction per day continuously for 14 days. The number of total cells continued to increase exponentially till day 5, and reached a plateau level thereafter. The cell cycle distribution changed marginally for the first 5 days, and showed a prominent G2/M accumulation at day 7. Plating efficiencies decreased exponentially with increasing fractionation while the total clonogenic cell number remained constant until day 4. Radiosensitivity at each fraction was stable until day 9, but significantly increased at day 11. A comparison of plating efficiencies between the immediate and 24-h delayed assays revealed that the capacity of cells to spare 2-Gy damage increased with the number of 2-Gy fractions. These results suggest that sublethal damage could accumulate during multifraction daily irradiations, while repair of potentially lethal damage and/or proliferation could rather increase.

Carcinoma, Squamous Cell↗

Anti-inflammatory effects of sulfatides in selectin-dependent acute lung injury.

Selectins promote adhesive interactions between leukocytes and activated endothelial cells, the adhesion being mediated by 'counter-receptors' on endothelial cells and consisting of oligosaccharide conjugates containing sialic acid and fucose. There are also suggestions that selectins bind sulfated compounds, including sulfatides. Intravenous infusion of selectin-reactive oligosaccharides has been found to prevent selectin-dependent inflammatory lung injury. In the current studies using two models of neutrophil and selectin-dependent acute lung injury in rats, sulfatide and its modified versions were infused i.v. and the protective effects determined. Naturally occurring sulfatide, synthetic sulfatides and sulfated ganglioside were highly protective against lung injury following systemic activation of complement. Desulfated sulfatide was inactive. The protective effects of synthetic sulfatides required sulfation of galactose in position 3. Sulfatide was also protective in the IgG immune complex model of lung injury. The protective effects of sulfatides were associated with reduced content of myeloperoxidase (derived from neutrophils) in lung tissue. These data indicate that sulfatides have significant in vivo protective effects in neutrophil and selectin-dependent models of lung injury.

Animals↗